Abstract
Introduction: Hearing loss is a common sensory disorder that impacts patients across the lifespan. Many genetic variants have been identified that contribute to non-syndromic hearing loss. Yet, genetic testing is not routinely administered when hearing loss is diagnosed, particularly in adults. In this study, genetic testing was completed in patients with known hearing loss. Methods: A total of 104 patients who were evaluated for hearing loss were enrolled and received genetic testing. Results: Of those 104 patients, 39 had available genetic testing, 20 had one missing allele, and 45 yielded no genetic diagnosis. Of the 39 cases with genetic testing data, 24 were simplex cases, and 15 were multiplex cases. A majority of patients presented with an autosomal recessive inheritance pattern (n = 32), 26 of whom presented with congenital hearing loss. 38% of cases were positive for GJB2 mutation with c.35delG being the most common pathogenic variant. These findings are consistent with previous literature suggesting GJB2 mutations are the most common causes of non-syndromic hearing loss. Conclusion: Given the frequency of genetic variants in patients with hearing loss, genetic testing should be considered a routine part of the hearing loss work-up, particularly as gene therapies are studied and become more widely available. Lay Summary: Many genetic variants have been identified that contribute to non-syndromic hearing loss. Given the frequency of genetic variants in patients with hearing loss, genetic testing should be considered a routine part of the hearing loss work-up.
Journal Section:
Research Article
References
1.
Van Camp
G
, Smith
RJ
. The hereditary hearing loss homepage
. J Audiological Medicine International Assoc Physicians Audiology London
. 1997
;6
:3
–5
.2.
Azaiez
H
, Booth
KT
, Ephraim
SS
, Crone
B
, Black-Ziegelbein
EA
, Marini
RJ
, et al. Genomic landscape and mutational signatures of deafness-associated genes
. Am J Hum Genet
. 2018
;103
(4
):484
–97
. 3.
Parker
M
, Bitner-Glindzicz
M
. Genetic investigations in childhood deafness
. Arch Dis Child
. 2015
;100
(3
):271
–8
. 4.
Sloan-Heggen
CM
, Bierer
AO
, Shearer
AE
, Kolbe
DL
, Nishimura
CJ
, Frees
KL
, et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss
. Hum Genet
. 2016
;135
(4
):441
–50
. 5.
Shearer
AE
, Shen
J
, Amr
S
, Morton
CC
, Smith
RJ
, Newborn Hearing Screening Working Group of the National Coordinating Center for the Regional Genetics Networks
. A proposal for comprehensive newborn hearing screening to improve identification of deaf and hard-of-hearing children
. Genet Med
. 2019
;21
(11
):2614
–30
. 6.
Avraham
KB
, Kanaan
M
. Genomic advances for gene discovery in hereditary hearing loss
. J Basic Clin Physiol Pharmacol
. 2012
;23
(3
):93
–7
. 7.
Mahdieh
N
, Rabbani
B
. Statistical study of 35delG mutation of GJB2 gene: a meta-analysis of carrier frequency
. Int J Audiol
. 2009
;48
(6
):363
–70
. 8.
Simpson
AN
, Matthews
LJ
, Cassarly
C
, Dubno
JR
. Time from hearing aid candidacy to hearing aid adoption: a longitudinal cohort study
. Ear Hear
. 2019
;40
(3
):468
–76
. 9.
UK NGC
. Hearing loss in adults: assessment and management
. 2018
.10.
Nassiri
AM
, Ricketts
TA
, Carlson
ML
. Current estimate of hearing aid utilization in the United States
. Otol Neurotol Open
. 2021
;1
(1
):e001
. 11.
Nassiri
AM
, Sorkin
DL
, Carlson
ML
. Current estimates of cochlear implant utilization in the United States
. Otol Neurotol
. 2022
;43
(5
):e558
–62
. 12.
Butcher
E
, Dezateux
C
, Cortina-Borja
M
, Knowles
RL
. Prevalence of permanent childhood hearing loss detected at the universal newborn hearing screen: systematic review and meta-analysis
. PLoS One
. 2019
;14
(7
):e0219600
. 13.
American Academy of Pediatrics Joint Committee on Infant Hearing
, Harrison
J
, Chappell
J
. Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs
. Pediatrics
. 2007
;120
(4
):898
–921
. 14.
Organization WH
. World report on hearing
. World Health Organization
; 2021
.15.
Croll
PH
, Vinke
EJ
, Armstrong
NM
, Licher
S
, Vernooij
MW
, Baatenburg de Jong
RJ
, et al. Hearing loss and cognitive decline in the general population: a prospective cohort study
. J Neurol
. 2021
;268
(3
):860
–71
. 16.
Livingston
G
, Sommerlad
A
, Orgeta
V
, Costafreda
SG
, Huntley
J
, Ames
D
, et al. Dementia prevention, intervention, and care
. Lancet
. 2017
;390
(10113
):2673
–734
. 17.
Richards
S
, Aziz
N
, Bale
S
, Bick
D
, Das
S
, Gastier-Foster
J
, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of medical genetics and Genomics and the association for molecular Pathology
. Genet Med
. 2015
;17
(5
):405
–24
. 18.
Chen
S
, Francioli
LC
, Goodrich
JK
, Collins
RL
, Kanai
M
, Wang
Q
, et al. A genomic mutational constraint map using variation in 76,156 human genomes
. Nature
. 2024
;625
(7993
):92
–100
. 19.
Sobe
T
, Vreugde
S
, Shahin
H
, Berlin
M
, Davis
N
, Kanaan
M
, et al. The prevalence and expression of inherited connexin 26 mutations associated with nonsyndromic hearing loss in the Israeli population
. Hum Genet
. 2000
;106
(1
):50
–7
. 20.
Ma
Y
, Xiao
Y
, Bai
X
, Zhang
F
, Zhang
D
, Xu
X
, et al. GJB2, SLC26A4, and mitochondrial DNA12S rRNA hot-spots in 156 subjects with non-syndromic hearing loss in Tengzhou, China
. Acta Otolaryngol
. 2016
;136
(8
):800
–5
. 21.
Jiang
Y
, Huang
S
, Deng
T
, Wu
L
, Chen
J
, Kang
D
, et al. Mutation spectrum of common deafness-causing genes in patients with non-syndromic deafness in the Xiamen Area, China
. PLoS One
. 2015
;10
(8
):e0135088
. 22.
Usami
S-I
, Nishio
S-Y
, Nagano
M
, Abe
S
, Yamaguchi
T
, Deafness Gene Study Consortium
. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study
. PLoS One
. 2012
;7
(2
):e31276
. 23.
Masmoudi
S
, Elgaied-Boulila
A
, Kassab
I
, Ben Arab
S
, Blanchard
S
, Bouzouita
JE
, et al. Determination of the frequency of connexin26 mutations in inherited sensorineural deafness and carrier rates in the Tunisian population using DGGE
. J Med Genet
. 2000
;37
(11
):e39
. 24.
Ghasemnejad
T
, Shekari Khaniani
M
, Zarei
F
, Farbodnia
M
, Mansoori Derakhshan
S
. An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population
. Int J Pediatr Otorhinolaryngol
. 2017
;97
:113
–26
. 25.
Dahl
H-HM
. Prevalence and nature of connexin 26 mutations in children with non-syndromic deafness
. Med J Aust
. 2004
;181
(8
):437
. 26.
Kim
SY
, Kim
AR
, Han
KH
, Kim
MY
, Jeon
EH
, Koo
JW
, et al. Residual hearing in DFNB1 deafness and its clinical implication in a Korean population
. PLoS One
. 2015
;10
(6
):e0125416
. 27.
Park
JH
, Kim
NK
, Kim
AR
, Rhee
J
, Oh
SH
, Koo
JW
, et al. Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication
. Orphanet J Rare Dis
. 2014
;9
:167
–14
. 28.
Imtiaz
F
, Taibah
K
, Ramzan
K
, Bin-Khamis
G
, Kennedy
S
, Al-Mubarak
B
, et al. A comprehensive introduction to the genetic basis of non-syndromic hearing loss in the Saudi Arabian population
. BMC Med Genet
. 2011
;12
:91
–6
. 29.
Samanich
J
, Lowes
C
, Burk
R
, Shanske
S
, Lu
J
, Shanske
A
, et al. Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment
. Am J Med Genet
. 2007
;143A
(8
):830
–8
. 30.
Santos
R
, Wajid
M
, Pham
T
, Hussan
J
, Ali
G
, Ahmad
W
, et al. Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non‐syndromic hearing impairment
. Clin Genet
. 2005
;67
(1
):61
–8
. 31.
Nahili
H
, Ridal
M
, Boulouiz
R
, Abidi
O
, Imken
L
, Rouba
H
, et al. Absence of GJB3 and GJB6 mutations in Moroccan familial and sporadic patients with autosomal recessive non-syndromic deafness
. Int J Pediatr Otorhinolaryngol
. 2008
;72
(11
):1633
–6
. 32.
Kabahuma
RI
, Ouyang
X
, Du
LL
, Yan
D
, Hutchin
T
, Ramsay
M
, et al. Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population
. Int J Pediatr Otorhinolaryngol
. 2011
;75
(5
):611
–7
. 33.
Beheshtian
M
, Babanejad
M
, Azaiez
H
, Bazazzadegan
N
, Kolbe
D
, Sloan-Heggen
C
, et al. Heterogeneity of hereditary hearing loss in Iran: a comprehensive review
. Arch Iran Med
. 2016
;19
(10
):720
–8
.34.
Naghavi
A
, Nishimura
C
, Kahrizi
K
, Riazalhosseini
Y
, Bazazzadegan
N
, Mohseni
M
, et al. GJB2 mutations in Baluchi population
. J Genet
. 2008
;87
(2
):195
–7
. 35.
M Hashemzadeh
C
, Dd
F
, Ma
P
. Familial and sporadic GJB2-related deafness in Iran: review of gene mutations
. 2007
.36.
Yuan
Y
, You
Y
, Huang
D
, Cui
J
, Wang
Y
, Wang
Q
, et al. Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China
. J Transl Med
. 2009
;7
:79
–12
. 37.
Zazo Seco
C
, Wesdorp
M
, Feenstra
I
, Pfundt
R
, Hehir-Kwa
JY
, Lelieveld
SH
, et al. The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands
. Eur J Hum Genet
. 2017
;25
(3
):308
–14
. 38.
Nishio
S-Y
, Usami
S-I
. Outcomes of cochlear implantation for the patients with specific genetic etiologies: a systematic literature review
. Acta Otolaryngol
. 2017
;137
(7
):730
–42
. 39.
Shearer
AE
, Hansen
MR
. Auditory synaptopathy, auditory neuropathy, and cochlear implantation
. Laryngoscope Investig Otolaryngol
. 2019
;4
(4
):429
–40
. 40.
Nisenbaum
E
, Prentiss
S
, Yan
D
, Nourbakhsh
A
, Smeal
M
, Holcomb
M
, et al. Screening strategies for deafness genes and functional outcomes in cochlear implant patients
. Otol Neurotol
. 2021
;42
(1
):180
–7
. © 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2024
You do not currently have access to this content.
